The proposed project is designed to investigate the role of cell-cell interaction in the regulation of adult (HB A) and fetal (Hb F) hemoglobin synthesis by adult human erythroid precursors (BFU-E) in vitro. Specifically the ability of various cell populations, present in blood, to modulate bone marrow and blood BFU-E growth and synthesis of Hb A and Hb F will be studied. Cells obtained from blood will be fractionated by several methods including density centrifugation and velocity sedimentation. Enriched and/or pure cell populations will be tested for their ability to stimulate or inhibit BFU-E in plasma clot cultures. Stimulatory and inhibitory cell populations will be used to prepare conditioned medium, the effect of which will also be tested in plasma clot cultures. The effects of fractionated cells and their conditioned medium on BFU-E will be assessed by colony counts and radioimmune assays of Hb A and Hb F. The ultimate objective of this research is to extrapolate the collected data to an understanding of in vivo physiologic mechanisms and to suggest ways in which the production of Hb F may be reactivated in the adult. At the very least, a new systematic approach to in vitro erythropoiesis will emerge from the studies outlined.